Recommendations on health-related quality of life research to support labeling and promotional claims in the United States.

Health-related quality of life (HRQL) outcomes evaluation is becoming an important component of clinical trials of new pharmaceuticals and medical devices. HRQL research provides patients, providers, and decision makers with important information on the impact of disease and treatment on physical, psychological, and social functioning and well-being. These outcomes are also useful to the pharmaceutical and device industries as they attempt to understand and communicate product value to physicians, patients, health insurers and others. HRQL labeling and promotional claims in the US are likely to increase over the next few years. The evidentiary requirements to make such a claim should be based on accepted scientific standards of HRQL evaluation and consistent with the regulatory requirements for clinical efficacy. This report outlines the scientific practices that should be considered in the evaluation of evidence for an HRQL claim, including the selection of appropriate domains, evidence to support the reliability and validity of HRQL measurement, considerations in research design and statistical analyses, and the issue of clinical significance. Representatives from the pharmaceutical and device industries, regulatory agencies, and the HRQL scientific community should work together to make certain the use of HRQL in labeling and promotion are based on sound scientific evidence, and that these messages are clearly and accurately reported to the consumers.

Adaptation and evaluation of the Liverpool Seizure Severity Scale and Liverpool Quality of Life battery for American epilepsy patients.

The Liverpool Seizure Severity Scale (LSSS) and the Liverpool Quality of Life (LQOL) battery were developed in Great Britain to assess the severity of seizure symptoms and the impact of epilepsy on patients' quality of life. The scales have been validated on British patients, but have not been validated for use with American patients. The objectives of this study were to adapt the scales to the American population and to evaluate their reliability and validity. After modifications recommended by focus groups with patients and epilepsy specialists, the scales were administered to a sample of 90 epilepsy patients who had experienced seizures within the previous 4 weeks. Comparisons of patients with generalized tonic-clonic seizures (n = 58) and partial seizures (n = 32) revealed significant differences on 9 of the 20 items on the LSSS as well as the total score. None of the six LQOL subscales (negative drug effects, positive drug effects, affect balance, sense of mastery, life fulfilment and impact of epilepsy) distinguished patients with different seizure types but five of the six subscales were significantly correlated with seizure severity. The internal consistency and test-retest reliability were adequate for both the LSSS and LQOL. Finally, five of the six LQOL scales were significantly correlated with independent measures of mental health, physical health and role functioning.

Adaptation and evaluation of the Liverpool Seizure Severity Scale and Liverpool Quality of Life battery for American epilepsy patients.

The Liverpool Seizure Severity Scale (LSSS) and the Liverpool Quality of Life (LQOL) battery were developed in Great Britain to assess the severity of seizure symptoms and the impact of epilepsy on patients' quality of life. The scales have been validated on British patients, but have not been validated for use with American patients. The objectives of this study were to adapt the scales to the American population and to evaluate their reliability and validity. After modifications recommended by focus groups with patients and epilepsy specialists, the scales were administered to a sample of 90 epilepsy patients who had experienced seizures within the previous 4 weeks. Comparisons of patients with generalized tonic-clonic seizures (n = 58) and partial seizures (n = 32) revealed significant differences on 12 of the 20 items on the LSSS as well as the total score. None of the six LQOL subscales (negative drug effects, positive drug effects, affect balance, sense of mastery, life fulfillment and impact of epilepsy) distinguished patients with different seizure types but five of the six subscales were significantly correlated with seizure severity. The internal consistency and test-retest reliability were adequate for both the LSSS and LQOL. Finally, five of the six LQOL scales were significantly correlated with independent measures of mental health, physical health and role functioning.

The effect of mode of administration on medical outcomes study health ratings and EuroQol scores in AIDS.

Brief measures of health-related quality of life are being used with increased frequency in AIDS clinical trials. Self-administration of questionnaires can reduce costs in this setting because they require little time. However, the equivalence between self- and interview-administered responses in clinical trials is not known. We evaluated patient and proxy responses to the Medical Outcomes Study HIV Health Survey (MOS-HIV) and the EuroQol. We randomized 68 patients with advanced HIV disease on (1) mode of administration (self vs. interview); (2) type of interview (face-to-face vs. telephone); (3) questionnaire order (MOS-first vs. EuroQol-first); and (4) 2- vs. 3-item response categories for physical limitations. There were few differences in scores between self and interview administration and type of interview. Proxy respondents viewed patients as more impaired than did patients themselves on subjective aspects of health including mental health (63.8 vs. 75.7, p < 0.001), health distress (67.3 vs. 77.1, p = 0.007), pain (64.4 vs. 70.0, p = 0.04), and vitality (48.4 vs. 55.5, p = 0.04). Results concerning questionnaire order and number of response categories were not conclusive. Our results suggest that for patients with advanced HIV disease, data from the MOS-HIV and the EuroQol collected using different modes may be pooled, but that proxy responses should be calibrated.

Guidelines for reporting results of quality of life assessments in clinical trials.

Clinical trials involving quality of life measurement published in the literature suffer from important weaknesses due to the lack of information on numerous topics. The psychometric properties of the instruments are often lacking as well as data on the number of patients treated and analyzed. The handling of missing data is rarely documented. In order to facilitate the reporting of trials and the evaluation of published results, this article proposes a set of general guidelines for the reporting of clinical trials which include a quality of life assessment. A checklist designed to assist authors is appended.

A new instrument to assess the long-term quality of life effects from migraine: development and psychometric testing of the MSQOL.

Quality of life is important to persons experiencing migraine. This study discusses the development of a migraine-specific quality-of-life measure (MSQOL). Participants, who included migraineurs from both tertiary care centers and the community, were screened using the International Headache Society migraine criteria prior to enrollment. Internal consistency of the MSQOL was high (alpha 0.92). Reproducibility over an average of 24 days was high (intraclass correlation 0.90). Construct validity was determined by convergent validity and known groups validity. The MSQOL was compared to two other frequently used health status questionnaires; results indicate that the MSQOL more closely resembles well-being than functional status. Results also indicate that migraineurs with more symptoms, medical appointments per year to treat migraines, and migraine episodes per year have a significantly worse quality of life. The MSQOL proved valid and reliable as a self-administered measure and will be a useful tool in clinical migraine research. The information gained from its use in the clinical environment should provide important additional information about the impact of migraine on quality of life and the potential benefits of therapeutic interventions.

Measuring health-related quality of life in persons with genital herpes.

A disease-specific measure was needed for use in an international clinical trial to evaluate an investigational drug for genital herpes. A new measure was developed initially in the UK and translated and adapted for use in France, Italy, Germany, Denmark, Spain and the USA. This paper describes the translation and adaptation of the USA measure. It also describes the assessment of internal consistency, reproducibility, content validity, and construct validity (convergent and discriminant) of the measure. Two outcome measures of the final genital herpes-specific measure were developed: (1) a 21-item symptoms subscale; and (2) a 20-item HRQOL subscale. Each measure was scored and analyzed separately; the psychometric testing discussed in this paper refers to the HRQOL subscale only. The internal consistency of the HRQOL subscale is high (r = 0.93), as is the reproducibility measured with a two week interval (r = 0.85). Convergent validity is moderate to high. (Fleming Self-Regard subscale, r = 0.48; SF-36 Social Functioning dimension r = 0.59; SF-36 Mental Health dimension r = 0.50). The number of herpes outbreaks in the past year was a significant predictor of scores on the HRQOL subscale (0-1 outbreaks, mean = 82.1; 2+ outbreaks, mean = 72.1, p = 0.058) suggesting discriminant validity. The measure is currently in a phase III clinical trial including anti-viral therapy where the question of responsiveness can be addressed.

Estimating the value of a generic quality-of-life measure.

In this paper, data from a clinical trial of a new antiviral agent for treating patients with zoster are used to answer the following question: Does the Nottingham Health Profile (NHP) add to the information obtained from the clinical measures? Three ways in which the NHP could add information are measured. First, Cox's regression analysis is used to determine whether health-related quality-of-life scores obtained at diagnosis give information about disease prognosis. Second, changes in mean NHP scores in different dimensions are computed after pain resolution to determine whether NHP scores provide more sensitive indicators of disease resolution. Third, linear regression is used to determine whether the impacts of disease on quality of life are measured adequately by the clinical parameters. These analyses show that use of the physical mobility and energy dimensions of the NHP increases understanding of disease prognosis; demonstrates the continuing impact of zoster on patients' sleep patterns and energy levels, disease symptoms not included as clinical measures, that persist after the cessation of zoster-associated pain; and gives a measure of the impact of zoster on the patient, which includes unmeasured and measured levels of severity.

The Nottingham Health Profile as a measure of quality of life in zoster patients: convergent and discriminant validity.

The main symptoms of zoster, a disease caused by the reactivation of the varicella zoster virus (that causes chicken-pox) are: rash, associated with pain, burning, or itching, and pain that outlasts the rash sometimes by months or years. The uncomfortable and long-lasting symptoms of herpes zoster are likely to compromise the patient's quality of life. However, the impact of zoster on health-related quality of life has not previously been measured directly. Recent papers have demonstrated the ability of generic measures to discriminate among patients with different clinical symptoms. In this paper, we demonstrate the convergent validity for zoster of a generic measure, the Nottingham Health Profile (NHP), by measuring its correlation with rash progression, pain levels, and pain medications. The discriminant validity of the NHP was demonstrated by its ability to distinguish between different levels of pain severity. The NHP dimensions most highly correlated with the pain measures, were pain (0.42-0.50), energy (0.34-0.38) and sleep (0.32-0.38). The NHP scores in all six dimensions show large differences at different levels of pain severity that are statistically significant. These results demonstrate the NHP's validity as a measure of health-related quality of life in zoster patients.

Intellectual property considerations in the development and use of HRQL measures for clinical trial research.

As a result of the expanded use of health-related quality of life (HRQL) measures in clinical trial research, a variety of legal and ethical issues have surfaced. These issues can be put in the form of the following questions: (1) Under what circumstances should access to HRQL measures be restricted? (2) Under what circumstances is it appropriate for the developers of HRQL measures to assert their intellectual property rights to the instruments? (3) Under what circumstances is personal profit from the sale and use of HRQL measures legally and socially appropriate? Access to HRQL research is to be encouraged since this is necessary for this field to progress. However, the need for protection against misuse of ongoing work is real and may justify the assertion of intellectual property rights. HRQL measures developed entirely with public monies should remain in the public domain or be managed for the public good. Instruments developed with private funds or with a mix of public and private funds should be treated in a manner that reflects a fair balance between the rights of the private developer and those of the scientific community and the public. HRQL questionnaires are regularly being refined; such work is costly. Investigators continuing research directly related to instrument refinement might reasonably ask for compensation from those who wish to use their work.

[Clinico-functional studies in patients with bird fancier's lung]. / Klinisch-funktionelle Untersuchungen bei Patienten mit Vogelhalter-Lunge.

Bird fancier's lung is a typical manifestation of extrinsic allergic alveolitis. In 107 cases with etiologically and histologically verified diagnosis tests of pulmonary function and hemodynamics were performed at admission to hospital and after 2-3 years of allergen abstinence and therapy. Acute forms of disease show distinct functional improvement, while chronic forms lead to increasing impairment.

[Contribution to the assessment of physical fitness in patients with pulmonary diseases on the basis of cardiopulmonary and ergometric parameters (author's transl)]. / Beitrag zur Einschätzung des Leistungsrestes bei Patienten mit pulmonalen Erkrankungen auf der Grundlage kardiopulmonaler und ergometrischer Parameter.

In 270 patients with COLD, bronchial asthma, exogenic allergic alveolitis or fibrosis of the lung measurements of VC, FEV 1,0, Rt, RV, DL CO, CL, PO2 and PAP (by means of floating catheter) were made. Results of measurements at rest and during exercise were compared after statistical treatment in the above groups and their value with regard to the determination of physical fitness was appreciated.

[Comparative investigations to the epidemiology of chronic bronchitis in Erfurt and Riga (author's transl)]. / Vergleichende Untersuchungen zur Epidemiologie der chronischen Bronchitis in Erfurt und Riga.

Studies concerning the prevalence of chronic bronchitis were conducted in Erfurt in 1971 and in Riga in 1974, comprising a standard interview and measurements of vital capacity and forced expiratory volume. Results in both towns are compared and critically discussed. Chronic bronchitis and obstruction are more frequent in Riga, while obstruction shows a better correlation to the severity of clinical signs in Erfurt. The influence of age, smoking, and hemoptysis are also compared; the latter showing no difference between both towns.

Continuous ambulatory peritoneal dialysis and pulmonary function.

Ten end-stage renal disease patients treated by continuous peritoneal dialysis were investigated by means of spirography, compliance tests, body plethysmography, and blood oxygen analysis. The ventilatory function was compared with abdomen empty and abdomen filled with 2L of peritoneal dialysis solution. Only a mild ventilatory restriction occurred (vital capacity -3.5%, thoracic gas volume -7.9%) as well as a mild decrease of static absolute compliance (-8.8%) and of dynamic absolute compliance (-6.2%). There was no significant alteration of the specific compliance tests, or of the Tiffeneau test as a parameter of bronchial obstruction, and no reduction of blood oxygen. These results were obtained from probands without bronchopulmonary illnesses. But problems with CAPD and ventilatory function may arise in patients with diseases of the respiratory tract including fluid lung, or in patients with 'space problems' in the abdomen (polycystic renal disease).

[Frequency of disturbances of pulmonary function in 4 cities of the GDR (author's transl)]. / Häufigkeitsverteilung pulmonaler Funktionsstörungen in vier Grossttädten der DDR

8369 men aged 35-64 were surveyed in 4 cities. The levels of FVC, FEV, pO2a were examined in connection with the standard questionnaire. The problems of lung function testing in epidemiological studies are discussed.